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    The EU Clinical Trials Register currently displays   42884   clinical trials with a EudraCT protocol, of which   7063   are clinical trials conducted with subjects less than 18 years old.
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    Summary
    EudraCT Number:2016-000917-59
    Sponsor's Protocol Code Number:ARCAAT2001
    National Competent Authority:Ireland - HPRA
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2016-04-13
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedIreland - HPRA
    A.2EudraCT number2016-000917-59
    A.3Full title of the trial
    An Open-Label, Multi-dose, Phase 2 Study to Determine the Safety, Tolerability and Effect on Circulating and Intrahepatic Alpha-1 Antitrypsin Levels of ARC-AAT as evidenced by changes in liver biopsy in Patients with Alpha-1 Antitrypsin Deficiency (AATD)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A clinical trial to assess the safety and effects of a novel medicine intended for the treatment of patients with liver disease due to Alpha-1 Antitrypsin Deficiency (AATD)
    A.4.1Sponsor's protocol code numberARCAAT2001
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorArrowhead Pharmaceuticals, Inc
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportArrowhead Pharmaceuticals, Inc
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationArrowhead Pharmaceuticals, Inc
    B.5.2Functional name of contact pointSusan Boynton, Regulatory Affairs
    B.5.3 Address:
    B.5.3.1Street Address225 South Pasadena Avenue, Suite 1050
    B.5.3.2Town/ cityPasadena, California
    B.5.3.3Post code91101
    B.5.3.4CountryUnited States
    B.5.4Telephone number001 626304 3400
    B.5.5Fax number001626304 3401
    B.5.6E-mailsboynton@arrowheadpharma.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/15/1605
    D.3 Description of the IMP
    D.3.1Product nameARC-AAT Injection
    D.3.2Product code ARC-AAT
    D.3.4Pharmaceutical form Solution for injection/infusion
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPIntravenous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNAPI-AAT
    D.3.9.2Current sponsor codeAPI-AAT
    D.3.9.3Other descriptive nameAPI-AAT, AD00370, ARC-AAT, API drug Substance
    D.3.9.4EV Substance CodeSUB174330
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number52
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Alpha-1 Antitrypsin Deficiency related liver disease
    E.1.1.1Medical condition in easily understood language
    Alpha-1 Antitrypsin Deficiency related liver disease
    E.1.1.2Therapeutic area Diseases [C] - Digestive System Diseases [C06]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 19.1
    E.1.2Level PT
    E.1.2Classification code 10001806
    E.1.2Term Alpha-1 anti-trypsin deficiency
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To determine the safety and tolerability of multiple doses of ARC-AAT Injection
    E.2.2Secondary objectives of the trial
    To determine the effect of multiple doses of ARC-AAT Injection on circulating levels of alpha-1 antitrypsin
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    To be eligible for enrollment, participants must meet all of the following inclusion criteria:
    1. Male or non-nursing female patients 18-75 years of age, inclusive, at the time of Screening with previous diagnosis of PiZZ genotype Alpha-1 Antitrypsin Deficiency. Availability of documented PiZ phenotype is sufficient to allow enrollment but a confirmatory genotype must be performed.
    2. Able and willing to provide written informed consent prior to the performance of any study specific procedures.
    3. Participants with a BMI between 18.0 and 35.0 kg/m2, inclusive. Participants with BMI between 15-18 kg/m2 or between 35-40 kg/m2 may be enrolled at the PI’s discretion in consultation with Sponsor depending on co-morbidities.
    4. A 12-lead ECG at Screening that, in the opinion of the investigator, has no abnormalities that compromise participant’s safety in this study.
    5. Non-smoker (not a daily cigarette smoker) for at least 12 months with current non-smoking status confirmed by urine cotinine at screening. Patients may be on nicotine replacement (patch or gum).e-cigarettes (vapor) is not permitted. A positive urine cotinine result due to nicotine replacement is acceptable for enrollment at the discretion of the PI.
    6. Participants using highly effective, double barrier contraception (both male and female partners) during the study and for 3 months following the last dose of ARC-AAT Injection. Males must not donate sperm for at least 3 months post last dose of study treatment. Male partners of female patients and female partners of male patients must also use contraception, if they are of childbearing potential. Females of childbearing potential must have a negative urine pregnancy test at Screening and on Day 1 pre-dose. Females not of childbearing potential must be postmenopausal (defined as cessation of regular menstrual periods for at least 12 months), confirmed by follicle-stimulating hormone (FSH) level > 40 mIU/mL or as otherwise consistent with postmenopausal state based on lab reference ranges.
    • Using twice the normal protection of birth control by using a condom AND one other form from the following:
    • Birth control pills (The Pill)
    • Depot or injectable birth control
    • IUD (Intrauterine Device)
    • Birth Control Patch (e.g., Othro Evra)
    • NuvaRing®
    • Surgical sterilization. i.e., tubal ligation, hysterectomy, bilateral oophorectomy, vasectomy or equivalently effective surgical form of birth control. Rhythm methods will not be considered as highly effective methods of birth control.
    7. Participants who are willing and able to comply with all study assessments and adhere to the protocol schedule
    8. Must have suitable venous access for blood sampling
    9. No abnormal finding of clinical relevance at the Screening evaluation that in the opinion of the investigator could adversely impact subject safety during the study or adversely impact study results.
    10. ALT, AST levels less than 5X times the upper limit of normal at Screening
    11. Creatinine levels < 1.5X upper limit of normal and estimated (calculated) GFR > or equal to 60 at Screening
    E.4Principal exclusion criteria
    A potential participant will be excluded from the study if any of the following criteria apply:
    1. INR > 1.3. If based on opinion of PI and/or prescribing physician patient is appropriate for anticoagulant holiday, patient may stop taking anticoagulant for an appropriate washout period and if indicated a repeat INR within < 1.3 would be acceptable. If INR is not indicated (direct thrombin inhibitors or Xa inhibitors) then appropriate washout period alone may be acceptable.
    (Note: Anti-platelet agents aspirin, clopidogrel or NSAIDS are acceptable but must be held 7 days before and 7 days after liver biopsy)
    2. Platelet count < 70,000
    3. A known diagnosis of hepatic fibrosis from a cause other than AATD (such as non-alcoholic steatohepatitis, alcoholism or infection)
    4. A history of poorly controlled autoimmune disease, or any history of autoimmune hepatitis
    5. Human immunodeficiency virus infection, as shown by the presence of anti-HIV antibody (seropositive)
    6. Seropositive for HBV or HCV
    7. Uncontrolled hypertension (Systolic BP > 170 and diastolic BP >100 mmHg at Screening)
    8. A history of torsades de pointes, ventricular rhythm disturbances (e.g., ventricular tachycardia or fibrillation), pathologic sinus bradycardia (<50 bpm and symptomatic), heart block (excluding first-degree block, being PR interval prolongation only), congenital long QT syndrome or new ST segment elevation or depression or new Q wave on ECG. Participants with a history of atrial arrhythmias should be discussed with the Medical Monitor
    9. A family history of congenital long QT syndrome or unexplained sudden cardiac death
    10. Symptomatic heart failure (per NYHA guidelines), unstable angina, myocardial infarction, severe cardiovascular disease (ejection fraction < 20%, transient ischemic attack (TIA) or cerebrovascular accident (CVA) within 6 months prior to study entry
    11. History of malignancy within the last 2 years except for adequately treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer. Participants with other curatively treated malignancies who have no evidence of metastatic disease and >1 year disease-free interval may be entered following approval by the Medical Monitor
    12. History of major surgery within 1 month of Screening
    13. Regular use of alcohol within one month prior to the Screening visit (i.e., more than fourteen units of alcohol per week [1 Unit = 150 mL of wine, 360 mL of beer, or 45 mL of 40% alcohol])
    14. Use of illicit drugs (such as cocaine, phencyclidine [PCP] and crack) within 1 year prior to the
    Screening visit or positive urine drug screen at Screening (a urine drug screen positive for benzodiazepines, opioids or marijuana is acceptable for enrollment at the discretion of the PI)
    15. History of known allergy to bee venom, any history of anaphylaxis or any history of severe systemic hypersensitivity reaction
    16. Use of an investigational agent or device within 30 days prior to dosing or current participation in an investigational study involving a therapeutic intervention. Subjects who have participated in the ARCAAT-1001 study or observational studies are acceptable.
    17. Any clinically significant history or presence of poorly controlled or decompensated neurological, endocrinal, cardiovascular, pulmonary, hematological, immunologic, psychiatric, metabolic or other uncontrolled systemic disease.
    18. Blood donation (≥500 mL) within 7 days prior to study treatment administration.
    19. Any concomitant medical or psychiatric condition or social situation that would make it difficult to comply with protocol requirements or put the participant at additional safety risk
    20. A history of thromboembolic disease (including deep vein thrombosis or pulmonary embolism), myocardial infarction, stroke within six (6) months of screening.
    21. Participants who are unable to return for all scheduled study visits
    22. Any other condition, that in the opinion of the investigator would render the participant unsuitable for enrollment, or could interfere with participating in and completing the study
    23. FEV1 at baseline < 50% (this criterion is only applicable if not on AAT augmentation therapy.
    For subjects on augmentation therapy FEV1 < 30% will be exclusionary). Pertinent study FEV1 will be based on post-bronchodilation value.
    24. AATD Patients with liver Elastography (i.e. FibroScan®) score > 12.5 at Screening
    25. Planned surgery requiring an induction agent (e.g. ketamine, etomidate) within 48 hours (both before and after) of IP administration.
    Note: Sponsor medical monitor has the option to exclude the enrollment of a participant if, based upon the participant’s medical history or Screening results, it is felt that a participant’s safety may be at risk.
    E.5 End points
    E.5.1Primary end point(s)
    Safety and tolerability of repeated doses of ARC-AAT Injection.

    E.5.1.1Timepoint(s) of evaluation of this end point
    See Schedule of Assessments
    E.5.2Secondary end point(s)
    Serum alpha-1 antitrypsin levels
    E.5.2.1Timepoint(s) of evaluation of this end point
    Pre-dose; Dosing Days 1, 29, 57, 85, 113, 141, 169; Days 197, 227, 257, 287 (EOS)
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Information not present in EudraCT
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA3
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Canada
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months6
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months6
    E.8.9.2In all countries concerned by the trial days0
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 11
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 1
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state6
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 6
    F.4.2.2In the whole clinical trial 12
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2016-06-10
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2016-06-29
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2016-11-29
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